Brain-first versus Body-first: Exploring aspects of gut microbiota in Parkinson’s disease

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dc.contributor.advisorMcCoy, Kathy
dc.contributor.authorKiani, Pardis
dc.contributor.committeememberSycuro, Laura
dc.contributor.committeememberMartino, Davide
dc.date2025-02
dc.date.accessioned2025-01-09T22:46:27Z
dc.date.available2025-01-09T22:46:27Z
dc.date.issued2025-01-08
dc.description.abstractParkinson’s disease (PD) is pathologically characterized by the irreversible aggregation of misfolded α-synuclein protein, forming what is known as Lewy Pathology, which is observed in multiple regions of the brain and gut. The “brain-first” and “body-first” hypothesis proposes distinct patterns of Lewy pathology distribution in the early stages of the disease, which categorizes clinical sub-phenotypes of PD. The “brain-first” sub-phenotype is thought to have predominant involvement of the amygdala, while the “body-first” sub-phenotype involves the enteric nervous system. In mouse models, the microbiota has been shown to be involved in promoting α-synuclein pathology and characteristic motor features in PD. This study aims to investigate whether microbiota from PD patients characterized as “brain-first” or “body-first” sub-phenotypes will induce divergent gastrointestinal functions and motor deficits in human microbiome-associated mice. Human PD microbiome-associated mice were generated by performing fecal microbial transfers from “brain-first” and “body-first” PD donors into germ-free C57BL/6 and dbl-PAC-Tg(SNCAA53T)Snca-/- recipient mice. FMT recipient mice were bred and gastrointestinal and motor functions in these offspring were analyzed. In dbl-PAC-Tg(SNCAA53T)Snca-/- mice, slow intestinal transit, indicative of decreased intestine motility, and increased gastrointestinal permeability were observed in “body-first” group compared to “brain-first” sub-phenotype. No significant motor function differences were detected between the two PD sub-phenotypes in these mouse models. Additionally, male dbl-PAC-Tg(SNCAA53T)Snca-/- “body-first” mice demonstrated a better ability to differentiate preferred odors in the olfactory preference test, whereas those colonized with microbiota from "brain-first" PD patients showed more olfactory dysfunction. Together, these results suggest that gut microbiota from PD patients may influence non-motor impairments associated with PD sub-phenotypes.
dc.identifier.citationKiani, P. (2025). Brain-first versus body-first: exploring aspects of gut microbiota in Parkinson’s disease (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/120403
dc.language.isoen
dc.publisher.facultyCumming School of Medicine
dc.publisher.institutionUniversity of Calgary
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectMicrobiome
dc.subjectParkinson's disease
dc.subjectGut microbiota
dc.subjectMice
dc.subjectNeurodegenerative diseases
dc.subject.classificationBioinformatics
dc.subject.classificationMicrobiology
dc.subject.classificationNeuroscience
dc.titleBrain-first versus Body-first: Exploring aspects of gut microbiota in Parkinson’s disease
dc.typemaster thesis
thesis.degree.disciplineMedicine – Microbiology & Infectious Diseases
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.thesis.accesssetbystudentI require a thesis withhold – I need to delay the release of my thesis due to a patent application, and other reasons outlined in the link above. I have/will need to submit a thesis withhold application.
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